ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.

Objective To propose a framework for risk assessment and stepwise management of pulmonary nodules based on existing guidelines and key studies, and to clarify the boundaries for triage, workup escalation, and referral in different detection scenarios. Methods A problem-oriented evidence synthesis approach was used, prioritizing Chinese expert consensus, Fleischner Society Guidelines, British Thoracic Society (BTS) Guidelines, and Lung-RADS. This was supplemented by studies on risk models, imaging measurements, liquid biopsy, tissue sampling, and surgical treatments. This paper is not presented as a formal consensus or a validated clinical pathway. Results A three-tiered framework consisting of basic non-invasive assessment, advanced assessment, and invasive diagnosis was established. It specified the applicable populations, boundaries for the use of risk models, imaging review, management of conflicting results, evaluation of histopathological consistency, and post-intervention follow-up. Liquid biopsy, genetic testing, and artificial intelligence were defined as investigational or adjunctive tools. Conclusion This framework can serve as a preliminary reference for multidisciplinary teams in developing local protocols. It cannot replace applicable guidelines, pathological diagnosis, shared decision-making with patients, or real-world validation.

Diabetic nephropathy （DN） is one of the most common and serious microvascular complications of diabetes mellitus and represents a major cause of chronic kidney disease progression and end-stage kidney disease， thereby constituting a major public health problem that adversely affects the prognosis and quality of life of patients with diabetes mellitus. The pathogenesis and progression of DN are complex and involve multiple pathological processes， including insulin resistance， inflammation， oxidative stress， lipid deposition， podocyte injury， and renal fibrosis. Although current clinical therapies can delay the progression of DN to some extent， their effectiveness remains limited by marked interindividual variability in therapeutic response and the difficulty of fully reversing renal injury. Therefore， further elucidation of the key molecular mechanisms underlying DN and the exploration of effective therapeutic strategies are of considerable importance. In recent years， with advances in the understanding of DN pathogenesis， peroxisome proliferator-activated receptor γ （PPARγ）， an important nuclear receptor transcription factor involved in the regulation of insulin resistance， inflammation， oxidative stress， and fibrotic processes， has attracted increasing attention for its role in the development and progression of DN. Traditional Chinese medicine （TCM）， characterized by multi-component， multi-target， and multi-pathway synergistic regulation， may ameliorate pathological processes including metabolic abnormalities， inflammation， oxidative stress， lipid deposition， and renal fibrosis in DN by targeting PPARγ and its associated signaling networks. This review systematically summarizes the mechanisms by which PPARγ and its related signaling pathways regulate DN and reviews recent advances in TCM interventions targeting the PPARγ signaling pathway in DN. Such TCM interventions encompass single herbs such as Coptidis Rhizoma， active constituents such as quercetin， astragaloside Ⅳ， and trigonelline， extracts of herbs such as Plantaginis Herba and Dendrobii Nobilis Caulis， and formulas such as Huangkui capsules， Shenshuaining granules， and Mudan granules. This review aims to provide a theoretical basis for the prevention and treatment of DN with TCM.

In this paper, near-infrared spectroscopy(NIRS) was employed to analyze 129 batches of commercial products of Reduning Injection. The batch reporting rate was estimated according to the report of Reduning Injection in the direct adverse drug reaction(ADR) reporting system of the drug marketing authorization holder of the Center for Drug Reevaluation of the National Medical Products Administration(National Center for ADR Monitoring) from August 2021 to August 2022. According to the batch reporting rate, the samples of Reduning Injection were classified into those with potential risks and those being safe. No processing, random oversampling(ROS), random undersampling(RUS), and synthetic minority over-sampling technique(SMOTE) were then employed to balance the unbalanced data. After the samples were classified according to appropriate sampling methods, competitive adaptive reweighted sampling(CARS), successive projections algorithm(SPA), uninformative variables elimination(UVE), and genetic algorithm(GA) were respectively adopted to screen the features of spectral data. Then, support vector machine(SVM), logistic regression(LR), k-nearest neighbors(KNN), naive bayes(NB), random forest(RF), and artificial neural network(ANN) were adopted to establish the risk prediction models. The effects of the four feature extraction methods on the accuracy of the models were compared. The optimal method was selected, and bayesian optimization was performned to optimize the model parameters to improve the accuracy and robustness of model prediction. To explore the correlations between potential risks of clinical use and quality test data, TreeNet was employed to identify potential quality parameters affecting the clinical safety of Reduning Injection. The results showed that the models established with the SVM, LR, KNN, NB, RF, and ANN algorithms had the F1 scores of 0.85, 0.85, 0.86, 0.80, 0.88, and 0.85 and the accuracy of 88%, 88%, 88%, 85%, 91%, and 88%, respectively, and the prediction time was less than 5 s. The results indicated that the established models were accurate and efficient. Therefore, near infrared spectroscopy combined with machine learning algorithms can quickly predict the potential risks of clinical use of Reduning Injection in batches. Three key quality parameters that may affect clinical safety were identified by TreeNet, which provided a scientific basis for improving the safety standards of Reduning Injection.
Spectroscopy, Near-Infrared/methods* ; Drugs, Chinese Herbal/administration & dosage* ; Machine Learning ; Algorithms ; Humans ; Quality Control

Acori Tatarinowii Rhizoma is the dried rhizome of Acorus tatarinowii in the family of Tennantiaceae, which has the efficacy of opening up the orifices and expelling phlegm, awakening the mind and wisdom, and resolving dampness and opening up the stomach. Modern studies have shown that volatile oil is the main active ingredient of Acori Tatarinowii Rhizoma, and α-asarone and β-asarone have been proved to be the active ingredients in the volatile oil of Acori Tatarinowii Rhizoma, with pharmacological effects such as anti-Alzheimer's disease, antiepileptic, anti-Parkinson's disease, antidepressant, anticerebral ischemia/reperfusion injury, anti-thrombosis, lipid-lowering, and antitumor. By summarising and outlining the pharmacological effects of α-asarone and β-asarone and elucidating the possible mechanisms of their pharmacological effects, we can provide theoretical basis for the further research and clinical application of Acori Tatarinowii Rhizoma.
Allylbenzene Derivatives ; Acorus/chemistry* ; Anisoles/chemistry* ; Rhizome/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Humans ; Animals

BACKGROUND: A growing body of research is exploring the role of antioxidant and anti-inflammatory dietary supplements in the treatment of osteoarthritis, highlighting an increasing emphasis on non-pharmacological interventions. Although more patients are turning to supplements to manage osteoarthritis, their actual effectiveness remains uncertain. OBJECTIVE: This study aims to provide a comprehensive evaluation of the available evidence concerning the efficacy of various dietary supplements in osteoarthritis treatment. SEARCH STRATEGY: We searched PubMed, Embase, Cochrane Library and Web of Science for studies on the use of various dietary supplements in the treatment of osteoarthritis from the creation of each database until Jan 20, 2025. INCLUSION CRITERIA: (1) Research object: osteoarthritis. (2) Intervention measures: patients in the treatment group received dietary supplements, while the control group received placebos. (3) Research type: randomized controlled trials (RCTs). DATA EXTRACTION AND ANALYSIS: Two researchers independently examined the literature and retrieved data based on predefined criteria. The information gathered included the first author, year of publication, sample size, participant demographics, length of the follow-up period, intervention and control measures, and inclusion indications. RCTs comparing dietary supplements to placebo with the pain and function subscales of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) among patients with osteoarthritis were included. The optimal dietary supplement was identified based on the total ranking by summing the surface under the cumulative ranking curve (SUCRA) of these two scores. Furthermore, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to confirm the quality of the evidence. RESULTS: Overall, 23 studies covering 21 dietary supplements and involving 2455 participants met the inclusion criteria. In the WOMAC pain score, the SUCRA of passion fruit peel extract was 91% (mean difference [MD]: -9.2; 95% confidence interval [CI]: [-16.0, -2.3]), followed by methylsulfonylmethane (89%), undenatured type II collagen (87%), collagen (84%), and Lanconone (82%). The SUCRA (99%) of passion fruit peel extract (MD: -41.0; 95% CI: [-66.0, -16.0]) ranked first in terms of the WOMAC function score, followed by Lanconone (95%), collagen (86%), ParActin (84%), and Lactobacillus casei strain Shirota (83%). The top three total rankings are passion fruit peel extract (95.0%), Lanconone (88.5%), and collagen (85.0%). However, the GRADE revealed low evidence quality. CONCLUSION Passion fruit peel extract was the best supplement for improving WOMAC pain and function scores in patients with osteoarthritis, followed by Lanconone and collagen. However, further large-scale, well designed RCTs are required to substantiate these promising findings. Please cite this article as: Chen CS, Wen L, Yang F, Deng YC, Ji JH, Chen RJ, Chen Z, Chen G, Gu JY. Effects of dietary supplements on patients with osteoarthritis: A systematic review and network meta-analysis. J Integr Med. 2025; 23(4): 357-369.
Humans ; Dietary Supplements ; Osteoarthritis/drug therapy* ; Randomized Controlled Trials as Topic

OBJECTIVE: To investigate the spatiotemporal patterns and socioeconomic factors influencing the incidence of tuberculosis (TB) in the Guangdong Province between 2010 and 2019. METHOD: Spatial and temporal variations in TB incidence were mapped using heat maps and hierarchical clustering. Socioenvironmental influencing factors were evaluated using a Bayesian spatiotemporal conditional autoregressive (ST-CAR) model. RESULTS: Annual incidence of TB in Guangdong decreased from 91.85/100,000 in 2010 to 53.06/100,000 in 2019. Spatial hotspots were found in northeastern Guangdong, particularly in Heyuan, Shanwei, and Shantou, while Shenzhen, Dongguan, and Foshan had the lowest rates in the Pearl River Delta. The ST-CAR model showed that the TB risk was lower with higher per capita Gross Domestic Product (GDP) [Relative Risk ( RR), 0.91; 95% Confidence Interval ( CI): 0.86-0.98], more the ratio of licensed physicians and physician ( RR, 0.94; 95% CI: 0.90-0.98), and higher per capita public expenditure ( RR, 0.94; 95% CI: 0.90-0.97), with a marginal effect of population density ( RR, 0.86; 95% CI: 0.86-1.00). CONCLUSION The incidence of TB in Guangdong varies spatially and temporally. Areas with poor economic conditions and insufficient healthcare resources are at an increased risk of TB infection. Strategies focusing on equitable health resource distribution and economic development are the key to TB control.
Humans ; China/epidemiology* ; Incidence ; Bayes Theorem ; Spatio-Temporal Analysis ; Tuberculosis/epidemiology* ; Socioeconomic Factors

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Hemoglobin, the principal protein in red blood cells, is crucial for oxygen transport in the bloodstream. The quantification of hemoglobin concentration is indispensable in medical diagnostics and health management, which encompass the diagnosis of anemia and the screening of various blood disorders. Immunological methods, based on antigen-antibody interactions, are distinguished by their high sensitivity and accuracy. Consequently, it is necessary to develop hemoglobin-specific antibodies characterized by high specificity and affinity to enhance detection accuracy. In this study, we immunized a Bactrian camel (Camelus bactrianus) with human hemoglobin and subsequently constructed a nanobody library. Utilizing a solid-phase screening method, we selected nanobodies and evaluated the binding activity of the screened nanobodies to hemoglobin. Initially, human hemoglobin was used to immunize a Bactrian camel. Following four immunization sessions, blood was withdrawn from the jugular vein, and a nanobody library with a capacity of 2.85×10⁸ colony forming units (CFU) was generated. Subsequently, ten hemoglobin-specific nanobody sequences were identified through three rounds of adsorption-elution-enrichment assays, and these nanobodies were subjected to eukaryotic expression. Finally, enzyme-linked immunosorbent assay and biolayer interferometry were employed to evaluate the stability, binding activity, and specificity of these nanobodies. The results demonstrated that the nanobodies maintained robust binding activity within the temperature range of 20-40 ℃ and exhibited the highest binding activity at pH 7.0. Furthermore, the nanobodies were capable of tolerating a 10% methanol solution. Notably, among the nanobodies tested, VHH-12 displayed the highest binding activity to hemoglobin, with a half maximal effective concentration (EC₅₀) of 10.63 nmol/L and a equilibrium dissociation constant (K_D) of 2.94×10^-7 mol/L. VHH-12 exhibited no cross-reactivity with a panel of eight proteins, such as ovalbumin and bovine serum albumin, while demonstrating partial cross-reactivity with hemoglobin derived from porcine, goat, rabbit, and bovine sources. In this study, a hemoglobin-specific high-affinity nanobody was successfully isolated, demonstrating potential applications in disease diagnosis and health monitoring.
Animals ; Camelus/immunology* ; Single-Domain Antibodies/immunology* ; Hemoglobins/immunology* ; Humans ; Peptide Library

Glutathione(GSH)is a tripeptide containing sulfhydryl groups,which has the function of antioxidant,detoxifying,and immune enhancing effects,and its expression is closely associated with many diseases such as cancer,etc.Therefore,it is of great significance for clinical diagnosis by developing a highly sensitive,simple,and rapid method for detecting GSH.Herein,two-dimensional(2D)Zn-TCPP(Fe)nanosheets employing Zn2+and Fe-bound tetrakis(4-carboxyphenyl)porphyrin ligands were obtained by a surfactant-assisted synthetic method.The 2D Zn-TCPP(Fe)nanosheets exhibited excellent peroxidase-like activity,which allowed the catalysis of the H2O2-initiated oxidation of colorless 3,3',5,5'-tetramethylbenzidine(TMB)to blue oxidized TMB(ox-TMB).In the presence of GSH,GSH underwent a reduction reaction with oxTMB,resulting in the blue color of the solution fading.The proposed colorimetric sensor exhibited favorable sensitivity for GSH in the linear range of 0.1-200 μmol/L with a limit of detection(S/N=3)of 0.042 μmol/L,indicating excellent selectivity.The developed sensor was successfully applied to detect GSH level in the human serum samples with recoveries of 93.0％-107.7％,showing satisfactory results.The developed colorimetric sensor provided a new approach for detecting GSH.